| First Author | Gollapudi SK | Year | 2016 |
| Journal | Arch Biochem Biophys | Volume | 601 |
| Pages | 105-12 | PubMed ID | 26792537 |
| Mgi Jnum | J:248762 | Mgi Id | MGI:6092783 |
| Doi | 10.1016/j.abb.2016.01.008 | Citation | Gollapudi SK, et al. (2016) The effect of cardiomyopathy mutation (R97L) in mouse cardiac troponin T on the muscle length-mediated recruitment of crossbridges is modified divergently by alpha- and beta-myosin heavy chain. Arch Biochem Biophys 601:105-12 |
| abstractText | Hypertrophic cardiomyopathy mutations in cardiac troponin T (TnT) lead to sudden cardiac death. Augmented myofilament Ca(2+) sensitivity is a common feature in TnT mutants, but such observations fail to provide a rational explanation for severe cardiac phenotypes. To better understand the mutation-induced effect on the cardiac phenotype, it is imperative to determine the effects on dynamic contractile features such as the muscle length (ML)-mediated activation against alpha- and beta-myosin heavy chain (MHC) isoforms. alpha- and beta-MHC are not only differentially expressed in rodent and human hearts, but they also modify ML-mediated activation differently. Mouse analog of human TnTR94L (TnTR97L) or wild-type TnT was reconstituted into de-membranated muscle fibers from normal (alpha-MHC) and transgenic (beta-MHC) mouse hearts. TnTR97L augmented myofilament Ca(2+) sensitivity by a similar amount in alpha- and beta-MHC fibers. However, TnTR97L augmented the negative impact of strained crossbridges on other crossbridges (gamma) by 22% in alpha-MHC fibers, but attenuated gamma by 21% in beta-MHC fibers. TnTR97L decreased the magnitude of ML-mediated recruitment of crossbridges (ER) by 37% in alpha-MHC fibers, but increased ER by 35% in beta-MHC fibers. We provide a mechanistic basis for the TnTR97L-induced effects in alpha- and beta-MHC fibers and discuss the relevance to human hearts. |
